Decreased miR-340 Expression in Bone Marrow is Associated with Liver Metastasis of Colorectal Cancer

Hiroshi Takeyama, Hirofumi Yamamoto, Shinya Yamashita, Xin Wu, Hidekazu Takahashi, Junichi Nishimura, Naotsugu Haraguchi, Yasuhiro Miyake, Rei Suzuki, Kohei Murata, Masayuki Ohue, Takeshi Kato, Ichiro Takemasa, Tsunekazu Mizushima, Hideshi Ishii, Koshi Mimori, Yuichiro Doki, Masaki Mori

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Abstract

Studies have shown the prognostic significance of disseminated tumor cells (DTC) in bone marrow of patients with colorectal cancer. However, the molecular characteristics of DTCs, including their miRNA expression profiles, remain mostly unknown. In this study, we analyzed the miRNA expression of DTCs in bone marrow. EpCAM+ bone marrow cells were collected using immunomagnetic beads after exclusion of CD14+ and CD45+ cells, then subjected to miRNA microarray analysis. Cluster analysis (7 colorectal cancer patients with liver metastasis and 12 colorectal cancer patients without liver metastasis) indicated that miR-340 and miR-542-3p expressions were significantly decreased in EpCAM+ bone marrow cells of patients with liver metastasis (P = 0.019 and 0.037, respectively). We demonstrated that pre-miR-340 administration inhibited growth of colon cancer cells and suppressed c-Met expression in vitro. In clinical samples of colorectal cancer, miR-340 was expressed at significantly lower levels in tumor tissues compared with normal mucosa. Survival analysis in 136 patients with colorectal cancer indicated that low miR-340 expression was correlated with shorter 5-year disease-free survival (P = 0.023) and poor 5-year overall survival (P = 0.046). It was of note that the colorectal cancer group with low miR-340 and high c-Met expression had the worst prognosis. We further demonstrated that systemic pre-miR-340 administration suppressed growth of pre-established HCT116 tumors in animal therapeutic models. These findings indicate that miR-340 may be useful as a novel prognostic factor and as a therapeutic tool against colorectal cancer. Our data suggest that miR-340 in bone marrow may play an important role in regulating the metastasis cascade of colorectal cancer. Mol Cancer Ther; 13(4); 976-85.

Original languageEnglish
Pages (from-to)976-985
Number of pages10
JournalMolecular Cancer Therapeutics
Volume13
Issue number4
DOIs
Publication statusPublished - Jan 1 2014

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Colorectal Neoplasms
Bone Marrow
Neoplasm Metastasis
Liver
MicroRNAs
Bone Marrow Cells
Neoplasms
Microarray Analysis
Survival Analysis
Growth
Colonic Neoplasms
Disease-Free Survival
Cluster Analysis
Mucous Membrane
Animal Models
Survival
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Decreased miR-340 Expression in Bone Marrow is Associated with Liver Metastasis of Colorectal Cancer. / Takeyama, Hiroshi; Yamamoto, Hirofumi; Yamashita, Shinya; Wu, Xin; Takahashi, Hidekazu; Nishimura, Junichi; Haraguchi, Naotsugu; Miyake, Yasuhiro; Suzuki, Rei; Murata, Kohei; Ohue, Masayuki; Kato, Takeshi; Takemasa, Ichiro; Mizushima, Tsunekazu; Ishii, Hideshi; Mimori, Koshi; Doki, Yuichiro; Mori, Masaki.

In: Molecular Cancer Therapeutics, Vol. 13, No. 4, 01.01.2014, p. 976-985.

Research output: Contribution to journalArticle

Takeyama, H, Yamamoto, H, Yamashita, S, Wu, X, Takahashi, H, Nishimura, J, Haraguchi, N, Miyake, Y, Suzuki, R, Murata, K, Ohue, M, Kato, T, Takemasa, I, Mizushima, T, Ishii, H, Mimori, K, Doki, Y & Mori, M 2014, 'Decreased miR-340 Expression in Bone Marrow is Associated with Liver Metastasis of Colorectal Cancer', Molecular Cancer Therapeutics, vol. 13, no. 4, pp. 976-985. https://doi.org/10.1158/1535-7163.MCT-13-0571
Takeyama, Hiroshi ; Yamamoto, Hirofumi ; Yamashita, Shinya ; Wu, Xin ; Takahashi, Hidekazu ; Nishimura, Junichi ; Haraguchi, Naotsugu ; Miyake, Yasuhiro ; Suzuki, Rei ; Murata, Kohei ; Ohue, Masayuki ; Kato, Takeshi ; Takemasa, Ichiro ; Mizushima, Tsunekazu ; Ishii, Hideshi ; Mimori, Koshi ; Doki, Yuichiro ; Mori, Masaki. / Decreased miR-340 Expression in Bone Marrow is Associated with Liver Metastasis of Colorectal Cancer. In: Molecular Cancer Therapeutics. 2014 ; Vol. 13, No. 4. pp. 976-985.
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AU - Takeyama, Hiroshi

AU - Yamamoto, Hirofumi

AU - Yamashita, Shinya

AU - Wu, Xin

AU - Takahashi, Hidekazu

AU - Nishimura, Junichi

AU - Haraguchi, Naotsugu

AU - Miyake, Yasuhiro

AU - Suzuki, Rei

AU - Murata, Kohei

AU - Ohue, Masayuki

AU - Kato, Takeshi

AU - Takemasa, Ichiro

AU - Mizushima, Tsunekazu

AU - Ishii, Hideshi

AU - Mimori, Koshi

AU - Doki, Yuichiro

AU - Mori, Masaki

PY - 2014/1/1

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N2 - Studies have shown the prognostic significance of disseminated tumor cells (DTC) in bone marrow of patients with colorectal cancer. However, the molecular characteristics of DTCs, including their miRNA expression profiles, remain mostly unknown. In this study, we analyzed the miRNA expression of DTCs in bone marrow. EpCAM+ bone marrow cells were collected using immunomagnetic beads after exclusion of CD14+ and CD45+ cells, then subjected to miRNA microarray analysis. Cluster analysis (7 colorectal cancer patients with liver metastasis and 12 colorectal cancer patients without liver metastasis) indicated that miR-340 and miR-542-3p expressions were significantly decreased in EpCAM+ bone marrow cells of patients with liver metastasis (P = 0.019 and 0.037, respectively). We demonstrated that pre-miR-340 administration inhibited growth of colon cancer cells and suppressed c-Met expression in vitro. In clinical samples of colorectal cancer, miR-340 was expressed at significantly lower levels in tumor tissues compared with normal mucosa. Survival analysis in 136 patients with colorectal cancer indicated that low miR-340 expression was correlated with shorter 5-year disease-free survival (P = 0.023) and poor 5-year overall survival (P = 0.046). It was of note that the colorectal cancer group with low miR-340 and high c-Met expression had the worst prognosis. We further demonstrated that systemic pre-miR-340 administration suppressed growth of pre-established HCT116 tumors in animal therapeutic models. These findings indicate that miR-340 may be useful as a novel prognostic factor and as a therapeutic tool against colorectal cancer. Our data suggest that miR-340 in bone marrow may play an important role in regulating the metastasis cascade of colorectal cancer. Mol Cancer Ther; 13(4); 976-85.

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